Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Genomics Proteomics Bioinformatics. 2020 Dec;18(6):708-720. doi: 10.1016/j.gpb.2020.06.013. Epub 2021 Feb 17.
Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.
肠道微生物群/肠激素轴的失调导致肠易激综合征（IBS）的发病机制。褪黑素在肠道动力和免疫中发挥有益作用。然而，IBS 中局部黏膜褪黑素的表达改变及其与肠道微生物群的关系尚不清楚。因此，我们旨在检测腹泻型肠易激综合征（IBS-D）患者的结肠褪黑素水平和微生物群谱，并在无菌（GF）大鼠和 BON-1 细胞中探索它们之间的关系。招募了 32 名 IBS-D 患者和 28 名健康对照者（HCs）。通过灌胃将 IBS-D 患者和 HCs 的粪便标本分别移植到 GF 大鼠中。通过免疫组织化学方法评估结肠黏膜褪黑素水平，通过 16S rDNA 测序分析粪便微生物群落。通过 ELISA 评估丁酸盐对 BON-1 细胞中褪黑素合成的影响。褪黑素水平在 IBS-D 患者中显著升高，与内脏高敏性呈负相关。接种来自 IBS-D 患者粪便微生物群的 GF 大鼠具有高结肠褪黑素水平。产丁酸的梭菌簇 XIVa 物种，如罗斯伯里氏菌和拉克诺普氏菌，与结肠黏膜褪黑素表达呈正相关。丁酸可显著增加 BON-1 细胞中褪黑素的分泌。褪黑素表达增加可能是 IBS-D 发展过程中的一种适应性保护机制。此外，一些梭菌簇 XIVa 物种可以通过产生丁酸来增加褪黑素的表达。调节肠激素/肠道微生物群轴为未来治疗 IBS 提供了一个有前途的研究目标。
